Programmed cell death protein 1 inhibition could be a valid option for patients with metastatic colorectal cancer that is DNA mismatch repair-deficient or microsatellite instability-high

medwireNews: Nivolumab elicits durable responses and is well tolerated by previously treated patients with metastatic colorectal cancer that is mismatch repair deficient (dMMR) or has high levels of microsatellite instability (MSI-H), shows the CheckMate 142 trial.

Of 74 patients with locally assessed dMMR/MSI-H disease who had progressed on or were intolerant to at least one prior therapy (including a fluoropyrimidine plus oxaliplatin
or irinotecan
), 31.1% achieved an investigator-assessed objective response to treatment with nivolumab 3 mg/kg every 2 weeks, while 69.0% had disease control for at least 12 weeks.

At the data cutoff after a median follow-up of 12 months, median duration of response had not been reached and all responders were alive, the research team reports. Three patients who initially responded experienced disease progression, but eight had responses that lasted 12 months or longer.

The findings were similar when the study authors focused on the 53 patients confirmed by central assessment to have dMMR/MSI-H disease, with an objective response rate of 36% and a disease control rate of 74%.

The programmed cell death protein 1 (PD-1) inhibitor was generally well tolerated and no new safety signals were observed, say Michael Overman, from The University of Texas MD Anderson Cancer Center in Houston, USA, and team.

Twenty percent of the 74 study participants experienced treatment-related toxicities of grade 3 or 4, most commonly elevated lipase (8%) and amylase (3%). Serious adverse events attributable to the drug occurred in 12%, and 7% discontinued treatment as a result of unacceptable toxicity.

“[N]ivolumab showed encouraging activity in patients with dMMR/ MSI-H tumours”, say the investigators, adding that “[t]he results from this phase 2 study confirm the clinical benefit of PD-1 inhibitor treatment in dMMR/MSI-H metastatic colorectal cancer and suggest that nivolumab is a new treatment option” for this patient population.

The author of a commentary accompanying the research in The Lancet Oncology agrees, saying that the CheckMate 142 results are “notable in view of the generally poor prognosis” of these patients.

Francesco Sclafani, from The Royal Marsden NHS Foundation Trust in Sutton, UK, continues: “Therefore, despite the small numbers and non-randomised study design, the results establish a new treatment option in this setting and confirm that MMR/MSI testing can no longer be considered as an ad-hoc screening procedure for genetic susceptibility or treatment selection in early-stage tumours, but should now be routinely offered to all patients with metastatic colorectal cancer.”